Treatment of seizures of partial origin in subjects with refractory epilepsy MedDRA version: 9.1 Level: LLT Classification code 10015037 Term: Epilepsy
Conditions
Sponsors
Supernus Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Capable of complying with the study procedures. 2) Able to provide written informed consent prior to any study procedure being conducted. 3) Male or female aged 18 to 65 years, inclusive. 4) Current diagnosis of partial onset seizures with or without secondarily generalized seizures as confirmed by the 1981 and 1989 International League Against Epilepsy [ILAE] Classifications. 5) Experiencing at least three countable partial seizures per 28 days on average during the eightweek Baseline Phase, or during the four-week Baseline plus the four-week period prior to Baseline, assuming the recording method is considered acceptable. Simple partial seizures in the Baseline Phase must have had an observable motor component. 6) Currently receiving treatment with at least one and up to three AEDs with AED therapy remaining at a stable dose for at least four weeks prior to Baseline (equivalent to 12 weeks prior to randomization). A vagal nerve stimulator (VNS) will be allowed, but will not be considered as one of the concomitant AEDs for the purpose of inclusion into the study. The VNS must have been implanted for at least six months prior to randomization. Stimulator parameters may not be changed for at least one month prior to screening (equivalent to 12 weeks prior to randomization) or during the study. Note, magnet use will be allowed, but must be documented throughout the study. 7) History of being refractory on at least one and up to three AEDs in single or combination use. 8) Magnetic resonance imaging (MRI), with or without contrast, or computerized tomography (CT), within the past 5 years showing no progressive neurological conditions. For subjects with MRI or CT older than 5 years, the MRI or CT can be performed in screening. 9) Use of prescription medications, except those specifically prohibited by protocol, and over-thecounter products, including natural food supplements, vitamins, garlic as a supplement, will be permitted as long as a stable dose has been maintained for four weeks prior to receiving study medication (SM). 10) Weight = 41kg. 11) Sexually active women, unless surgically sterile (at least 6 months prior to SM administration) or at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to SM administration] sexual partner) for at least four weeks prior to SM administration, and must agree to continue using such precautions through the End of Study visit. Cessation of birth control after this point should be discussed with a responsible physician. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) History of being refractory to OXC for reasons of efficacy based on 1200mg/day dose and 2-month trial period. 2) A documented history of generalized status epilepticus within the past 2 years. 3) A documented history of non-epileptic seizures in the past 2 years. 4) Seizures secondary to illicit drug or alcohol use, infection, neoplasia, demyelinating disease, degenerative neurological disease, or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease. 5) Diagnosis or an encephalogram consistent with a diagnosis of seizure disorders other than partial epilepsy. 6) Meets criteria for current major depressive episode, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision, within 6 months prior to Screening (Visit 1). 7) Current use of antidepressants. However, those subjects who are only taking a stable dose of either a selective serotonin reuptake inhibitor (SSRI) antidepressant drug or a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant drug for a diagnosed depressive disorder can be included as long as they have been on the SSRI or SNRI for a period of at least 56 days prior to randomization. Other antidepressant medications will not be allowed. 8) Active suicidal plan/intent or active suicidal thoughts in the past 6 month. 9) Suicide attempt within the last 2 years; 10) More than one lifetime suicide attempt. 11) History or presence of clinically significant, chronic medical condition, including hyponatremia, especially those contraindicating antiseizure medication (e.g., any neurological, gastrointestinal, endocrine, cardiovascular, pulmonary, hematological, immunologic, renal, hepatic, or metabolic disease) that may affect the safety of the subject in the opinion of the Investigator. 12) Current use of oxcarbazepine. 13) Phenytoin use is allowed if the subject is on a stable dose and the results of two consecutive serum phenytoin levels are 140 millimeters of mercury [mmHg], diastolic blood pressure [DBP] 90mmHg, or heart rate [HR] 100 beats per minute [BPM]) abnormalities at screening that may affect the safety of the subject, in the opinion of the Investigator. 18) Presence of potential hepatic function impairment as shown by, but not limited to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values >3 times upper limit of normal (ULN), or total bilirubin >1.5 ULN. 19) Presence of suspected impairment of renal function defined by serum creatinine =1.5 times ULN. 20) History of alcohol abuse within two years prior to the screening. 21) History of substance abuse or dependence within two years prior to screening. 22) Females who are pregnant or lactating. 23) Previous known hypersensitivity to OXC or other related drugs, such as carbamazepine, or any of the product components. 24) Use of an investigational drug or device, or participation in an investigational study within 30 days prior to the first dose of SM. 25) Difficulty s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of adjunctive OXC XR (Supernus Pharmaceuticals, Inc.) in the treatment of seizures of partial origin in subjects with refractory epilepsy on at least one and up to three other antiepileptic drugs (AEDs) in adults.;Secondary Objective: The secondary objectives are: • To assess the safety and tolerability of adjunctive OXC XR in the treatment of seizures of partial origin in subjects with refractory epilepsy on at least one and up to three other AEDs; • To assess the effect of OXC XR on the Subject’s Global Impression of Change in his/her epilepsy status; • To assess the effect of OXC XR on quality of life as assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31); and • To assess secondarily generalized seizures for each treatment group.;Primary end point(s): The percentage change (PCH) in partial seizure frequency per 28 days during the Treatment Phase (excluding the 3-week Tapering or Conversion Period) relative to the Baseline Phase in the ITT population. All partial seizures up to the point of subject discontinuation (excluding partial seizures during the 3-week Tapering or Conversion Period) will be included in the analysis. 28-day partial seizure frequency = (# partial seizures during the specified study phase/# days duringthe specified study phase) X 28 | — |
Countries
Bulgaria
Outcome results
None listed